The proposed studies attack unresolved questions about the fundamental organization of the cochlear spiral ganglion and its input to the brainstem. Using the cat as the animal model, certain inadequately substantiated concepts of the neuronal wiring of the mature cochlea will be re-examined. A combination of auditory evoked response, physiological microelectrode recording and cytochemical labeling techniques, along with extensive light and electron microscopic analysis will be employed. Special attention will be given to the morphology and connections of the small unmyelinated type II ganglion cells as contrasted with the more common type I cells: a) Ultrastructural characteristics of the neuronal processes of the two cell types will be defined in serial reconstructions of electron images; b) The differential projections of the two neuronal populations to specific cochlear nucleus subdivisions and cell fields will be further delineated; and 3) Individual neurons innervating inner and outer hair cells and labeled with horseradish peroxidase (HRP), will be traced and the fine structure of their parent sprial ganglion cells defined. In other experiments, the time course and sequence of ultrastructural pathological alternations in spiral ganglion cells secondary to destruction of the hair cells by neomycin sulfate will be examined, and the central projections of residual spiral ganglion cells in severely pathological cochleae will be delineated. These studies should provide a better understanding of factors precipatating cochlear neural degeneration and may have important implications re the efficacy of a cochlear implant in patients with parallel otic pathologies. Additionally, a vesicular transport in the hair cells will be further characterized in studies of HRP uptake from the perilymph. Evidence that HRP uptake may be activity dependent will be evaluated. Finally, a new cytochemical probe (neomycin conjugated to HRP and colloidal gold) will be employed to demonstrate the intracochlear sites of neomycin membrane receptors and to define membrane constituents responsible for calcium sequestration. These studies should contribute to out understanding of the cellular mechanisms of neomycin ototoxicity and provide new insight into the basic cell biology of mammalian hair cells.